en
Scientific article
English

TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk

Published inLaboratory investigation, vol. 79, no. 4, p. 495-500
Publication date1999
Abstract

Injection of mouse recombinant TNF to mice induced apoptosis and detachment of the enterocytes of the tip of the villi, evident after 30 to 90 minutes, which resulted in a shrinkage of the villi. Injection of TNF increased the expression of caspase 1, 2, 3, and 6 as well as of cathepsin D in the mucosal wall, which was maximal 30 minutes after TNF injection. Caspase 1 and 3 were not induced in TNFR1-deficient mice in which TNF does not induce apoptosis and detachment. The administration of a caspase inhibitor (ZVAD-fmk, 300 microg) decreased enterocyte detachment and apoptosis, as well as villus atrophy, whereas a caspase 3 inhibitor (Z-DEVD-cmk) had no effect. The results indicate that the induction of caspases by TNF is the cause of their detachment in the lumen and of the resulting villus atrophy.

Keywords
  • Amino Acid Chloromethyl Ketones/pharmacology
  • Animals
  • Antigens, CD/genetics/metabolism/physiology
  • Apoptosis/drug effects/physiology
  • Cell Adhesion/drug effects/physiology
  • Cysteine Proteinase Inhibitors/pharmacology
  • DNA Fragmentation
  • Intestinal Mucosa/cytology/drug effects/pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Receptors, Tumor Necrosis Factor/genetics/metabolism/physiology
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins/pharmacology
  • Tumor Necrosis Factor-alpha/pharmacology
Citation (ISO format)
PIGUET, Pierre et al. TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk. In: Laboratory investigation, 1999, vol. 79, n° 4, p. 495–500.
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Article (Published version)
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Identifiers
ISSN of the journal0023-6837
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